Stomatitis is defined as inflammation of the mucous membranes of the oral cavity and oropharynx characterized by tissue erythema, edema, and atrophy, often progressing to ulceration. Stomatitis is a biologically complex, multifactorial, treatment-related oral condition experienced by many oncology patients, which often leads to a cascade of negative sequelae including oropharyngeal pain, critical treatment alterations or cessation, and decreased quality of life. The optimal treatment strategies for stomatitis have not been established. There is a critical need to examine the pathogenesis of and to evaluate interventions for stomatitis and related acute oropharyngeal pain in the randomized controlled clinical trial setting using valid and reliable stomatitis assessment tools to both advance the science of cancer treatment-related oral toxicities and improve patient care. Therefore, the purpose of this randomized controlled clinical trial is to elucidate the role of inflammation in stomatitis by testing the effects of a novel tumor necrosis factor (TNF) fusion protein etanercept, (Enbrel?, Immunex Corporation, Seattle, WA) on the incidence and severity of stomatitis. The actions of this fusion protein, which binds specifically to TNF preventing its interaction with cellular receptors and altering the inflammatory cascade, may provide insight into the role of inflammation in stomatitis. An etanercept effect is defined as a prevention or amelioration of stomatitis and acute oropharyngeal pain and/or changes in levels of tissue mediators. If stomatitis is primarily a consequence of a mucosal inflammatory response, then we hypothesize that this oral condition will be responsive to binding of TNF-alpha. Elaboration of the role of inflammatory cell signalling associated with stomatitis and the effect of TNF-alpha may elucidate the mechanisms related to the pathogenesis of stomatitis and to other mucosal conditions. Patients who are scheduled to receive stomatogenic chemotherapy with autologous peripheral blood stem cell transplanation, ages 16 years or older, will be invited to participate in this study during a regularly scheduled pre-treatment visit in the National Institute of Dental and Craniofacial Research Dental Clinic, or through established recruitment strategies at a National Cancer Institute sponsored Community Clinical Oncology Program located at the Cancer Centers of the Carolinas, Greenville, SC. Written informed consent will be obtained from all participants. Patients will be randomized to receive either etanercept mouthwash or placebo, which will both be administered by protocol schedule. Stomatitis and oropharyngeal pain will be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course. TNF-alpha levels in buccal mucosa, analyzed by real time polymerase chain reaction techniques, and blood levels of pro-inflammatory cytokines, growth factors, and inflammatory mediators will also be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course. This study will begin to accrue subjects following the approval of the data and safety monitoring plan by the Data and Safety Monitoring Board, which convened in Augsut, 2005. The study transferred from the National Institute of Dental and Craniofacial Research to the National Institute of Nursing Research in 2004.